The brain is a sort of fortress, equipped with barriers designed to keep out dangerous pathogens. But protection comes at a cost: These barriers interfere with the immune system when faced with dire threats such glioblastoma, a deadly brain tumor for which there are few effective treatments. Many of these are trials of a “novel/investigational agent” – meaning it is the first time a particular treatment is being tried for brain tumor patients. There are also a number of trials with therapies already in use for some brain tumor patients – meaning researchers are evaluating these already-in-use treatments in different combinations, different dosing regimens, or subpopulations of patients. Some brain tumours grow very slowly (low grade) and cannot be cured. Depending on your age at diagnosis, the tumour may eventually cause your death. Or you may live a full life and die from something else. It will depend on your tumour type, where it is in the brain, and how it responds to treatment. Chemotherapy, radiation, and surgery have been considered treatment staples for glioblastoma for decades. However, many chemotherapy drugs are not able to reach the brain and there are no specific treatments that can kill all the cancerous cells. Because of this, the tumour usually grows back within six to nine months of initial diagnosis and treatment.
Brain tumors have been some of the most challenging types of cancers. A protective barrier around the brain—called the “blood-brain barrier”—can prevent cancer treatments from reaching the tumor. Recently, increased interest in immunotherapy has given new hope to getting through this barrier. The IDH1 gene is mutated in about half of gliomas, the most common type of brain cancer. These tumors tend to be low-grade and occur at a younger age. Survival can be seven to 10 years. Adding a drug that inhibits a critical pathway in DNA damage repair made the tumors sensitive to radiation treatment. Researchers initially discovered this using the newly-created mutant IDH1 mouse models and confirmed their findings in tissue samples from patients with IDH1-mutant glioma.
In recent years, researchers have found some changes in genes, chromosomes, and proteins inside brain tumor cells that can be used to help predict a person’s outlook (prognosis) or help guide treatment. Some examples of changes that can now be tested for include:
Enhanced imaging tests: New techniques for imaging scans are being researched. These may help doctors better track how well treatment is working and watch for possible tumor recurrence or growth.
Biomarkers: Researchers are examining biomarkers that may help diagnose a brain tumor, estimate a patient’s prognosis, and/or predict whether a specific treatment may work.
Immunotherapy: Immunotherapy, also called biological response modifier (BRM) therapy, is designed to boost the body’s natural defenses to fight the tumor. It uses materials either made by the body or in a laboratory to improve, target, or restore immune system function. Different methods are being studied for brain tumors, such as the use of dendritic cells or the use of vaccines aimed against a specific molecule on the surface of the tumor cells. Several methods are currently being tested in clinical trials.
For this approach, the patient is given a special fluorescent dye a few hours before surgery. The dye is taken up by some tumors, which then glow when the surgeon looks at them under special lighting from the operating microscope. This lets the surgeon better separate the tumor from normal brain tissue. Researchers are now looking to improve on the dyes currently in use.
Oncolytic virus therapy: This therapy uses a virus that infects and destroys tumor cells, sparing healthy brain cells. It is currently being researched as a treatment for brain tumors.
This is a type of MRI test that can show where the major pathways (tracts) of white matter are in the brain. Surgeons can look at this information before operating to help avoid these important parts of the brain when removing tumors.
Targeted therapy: This type of treatment targets faulty genes or proteins that contribute to a tumor’s growth and development. Research continues on the use of therapies for brain tumors that target the different ways a tumor grows, how a tumor spreads, and how tumor cells die.
Blood-brain barrier disruption: This technique temporarily disrupts the brain’s natural protective barrier in order to allow chemotherapy to more easily enter the brain from the bloodstream.
For some tumors that are hard to treat surgically, another option might be to insert a thin probe with a tiny laser on the end through a small hole in the skull and into the tumor. The laser is then used to heat and destroy (ablate) the tumor. This technique is still fairly new, so doctors are still learning about the best ways to use it.
New drugs and combinations of drugs: Researchers are looking at using drugs currently available for other types of cancer as treatment for a brain tumor. In addition, combinations of drugs that target the different ways a tumor grows and spreads are being explored. Since tumors can develop resistance to chemotherapy, meaning the treatment stops working, another approach is to use a treatment that targets how tumor cells develop resistance.
Gene therapy: This type of therapy seeks to replace or repair abnormal genes that are causing or helping tumor growth.
As brain tumors grow in size, they can cause a wide variety of painful and life-altering symptoms for patients with the disease, often due to the pressure these tumors inflict on the brain or the ways in which the tumors interfere with normal, healthy brain and nerve function. The majority of brain cancers are highly invasive, though this disease rarely spreads to parts of the body beyond the brain. Although significant advances have been made in understanding the biology of these cancers—as well as in tumor diagnosis, treatments, and quality of life of patients with the disease—the mortality rate has remained steady for more than 30 years.